Safety Evaluation of Recombinant Human Interleukin-4☆

Abstract Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of preclinical studies. These studies have demonstrated that rhuIL-4 is a very potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liver, spleen, and bone marrow. The incidence and severity of effects correlated strongly with both the dose level and the duration of rhuIL-4 administration. The major dose-limiting toxicities identified included death, cardiac inflammation and necrosis, hepatitis, and hepatic necrosis and occurred at sc doses ≥25 μg/kg/day, while a sc dose of 5 μg/kg/day was the highest tested that did not result in major dose-limiting toxicity. Clinical trials in humans have demonstrated that sc administration of Escherichia coli -derived rhuIL-4 is safe and well tolerated at doses up to and including 5 μg/kg/day and up to 10 μg/kg when administered 3 times/week.